Our aim is to elucidate the process of intracellular protein degradation. In this connection we are pursuing two main lines of investigation. One consists of studies of uptake and degradation of liver proteins by liver parenchymal cells in culture. The rationale of this approach is to determine whether there is a selectivity in pinocytic uptake and delivery of these proteins to these lysosomal system, which may be a model for the autophagic uptake and translocation to the lysosome of the same proteins from the interim of the cell. In addition the procedure allows us to determine whether there is a selectivity in the degradation of liver proteins subsequent to their entry within the lysosome. The second set of studies involves the uptake and degradation by liver parenchymal cells of radiolabeled proteins of known amino acid sequence. We will attempt to identify intermediates in the breakdown of these proteins in order to determine the sequence of bond splitting and to identify the lysosomal cathepsins responsible for the individual proteolytic reactions.